Neurodegenerative disorders are progressive disorders to cause destructive damages such as the nerve cell death. As principal neurodegenerative disorders, there have been known central nervous system disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease and the like, and peripheral neuropathies represented by diabetic neuropathy. Many of them relate to aging and, in fact, the onset increases with aging, whereas there are also some cases in which the onset begins even at a middle age and further at a younger age.
As a result of studies on the structure and function of brains, the roles of neurotransmitters and neurotrophic factors and so on have been gradually elucidated, but many parts of the causes of neurodegenerative disease are still unknown. For Parkinson's disease, its relationship with a specific neurotransmitter, namely dopamine, has been clarified, whereby L-DOPA that is the precursor of dopamine has been used as a drug for reducing the nerve symptoms and for recovering the function. However, L-DOPA does not suppress the progress of neurodegeneration, and the effect of L-DOPA is gradually lost with a progress of the disease condition, namely the degeneration and loss of dopaminergic neurons. Also, Alzheimer's disease is a disorder that is caused by the degeneration and loss of a variety of nerve cells such as acetylcholinergic neuronal cells, monoamine type neuronal cells, and the like, and causes deposit of senile plaque or change in neurofibrils. As for the drugs therefor, cholinesterase inhibitors or memantine, which is an antagonist for NMDA, have been marketed. Nevertheless, like L-DOPA for Parkinson's disease, they are still symptomatic therapy to improve the nerve symptoms temporarily. In this regard, drugs that can protect neuronal cells from the toxicity of the factors causing cell death including Alzheimer's disease or Parkinson's disease and can inhibit progress of neurodegenerative disorders have not been reported.
Furthermore, it is considered that the cell death in neurodegenerative disorders is caused by the toxicity of the factors that are intrinsic to the respective diseases and, for example, in Alzheimer's disease, the endogenous β-amyloid is considered to be a factor to cause the cell death. β-Amyloid is a protein constituting the senile plaque, which is a neuropathological characteristic to be seen in brain of a patient suffering from Alzheimer's disease, and is composed of 40 to 43 amino acids. It has been found that the addition of this β-amyloid to a primary culture system of hippocampus nerve cell causes nerve cell death [see, Non-Patent Document No. 1] and, also, it has been shown that the coagulation of β-amyloid is indispensable for the expression of its toxicity and the like [see, Non-Patent Document Nos. 2 and 3]. For toxicity expression mechanism of β-amyloid, it has been believed that 1) β-amyloid forms an ion channel to allow an influx of calcium ions, 2) β-amyloid accelerates generation of free radicals, 3) β-amyloid activates tau protein kinase I (TPK-I)/glycogen synthase kinase 3 beta (GSK-3β) and promotes the phosphorylation of tau, 4) β-amyloid activates the microglia, from which the neurotoxin is secreted, and the like. Recently, it has been elucidated that neurotrophic factors such as IGF-1 (insulin-like growth factor), NGF (nerve growth factor), BDNF (brain derived neurotrophic factor), GDNF (glial cell line derived neurotrophic factor) and the like inhibit the apoptosis of nerve cells caused by β-amyloid and cell death (apoptosis) is caused by dysfunction of nutritional factor signal cascade [see, Non-Patent Document No. 4]. With respect to them, it has been reported that IGF-1 (insulin-like growth factor 1) signal phosphorylates Akt, also referred to as protein kinase B (PKB), via phosphatidylinositol-3′-kinase (PI-3 kinase: PI-3K), and the activated Akt phosphorylates a substrate like Bad or glycogen synthase kinase 3b (GSK-3β) and the like to inhibit neuronal cell death. As a mechanism therefor, it becomes evident that inhibition of GSK-3β based on activation of PI-3 kinase is involved [see, Non-Patent Document Nos. 5 to 7]. When PI-3 kinase is inhibited by β-amyloid and TPK-I/GSK-3β is activated, pyruvate dehydrogenase (PDH) is inhibited, thereby affecting the synthetic reaction system of acetylcholine to lower the content of acetylcholine. This is in agreement with an observation that the content of acetylcholine is lowered in the brain of a patient suffering from Alzheimer's disease. On the contrary, it is expected that the activation of PI-3 kinase can accomplish not only the prevention of nerve cell death but also an increase in the content of acetylcholine in brain, thereby improving the nerve symptoms. In addition, it is expected that inhibition of TPK-I/GSK-3β can increase the intracerebral glucose utilization, which is lowered in Alzheimer's disease [see, Non-Patent Document Nos. 7 and 8]. Further, correlation between glucose metabolism in brain and cognitive function in brain was also reported [see, Non-Patent Document No. 9] and it is expected that improving the glucose metabolism in brain may also improve the cognitive function of the brain.
As a compound useful for the prophylaxis or treatment of central nervous system disorders or brain disorders, benzofuran compounds are publicly known (for example, see Patent Document Nos. 1 to 7). Further, it is also publicly known that some kinds of benzofuran compounds have an activity of promoting growth and differentiation of neuronal progenitor cells (for example, see Patent Document Nos. 2 and 4).
Still further, it is also publicly known that the benzofuran compounds have medical use other than the use for central nervous system disorders (for example, see Patent Document Nos. 8 and 9 and Non-Patent Document No. 10).
Non-Patent Document No. 10 discloses the following compound:

Specifications of respective Patent Documents should be referred for the definitions of the following compounds disclosed in Patent Document Nos. 10-16. Patent Document No. 10 discloses the following compound:

Patent Document No. 11 discloses the following compound:

Patent Document No. 12 discloses the following compound:

Patent Document No. 13 discloses the following compound:

Patent Document No. 14 discloses the following compound:

Patent Document No. 15 discloses the following compound:

Patent Document No. 16 discloses the following compound:

Patent Document No. 17 discloses the following compound:
